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Dec 30, 2015 11:48AM
Falls thought I would bring the doc letters here too :)
Sep 15, 2015 09:41AM - edited 22 minutes ago by sas-schatzi
Dear Doctor, I request that you give the material I've given you re: The use of Toradol pre-incision serious consideration. I have a vested interest in the prevention of recurrence of breast cancer. Please, do not refuse my request if you have not read this current compelling research. If they're is not an absolute contraindication for the use of Toradol in my case, I request it be used.
My mantra for medical and nursing information for decades has been " Just when you think you know something look again" I thought I was done searching for an answer yesterday on something else, then I listened, "You don't know enough, look again, you don't know enough look again". That pesky little irritating voice that drives me. I looked again and came upon the Retsky study. This is groundbreaking research as is the Forget study. A leap forward.
There has been ongoing research that is looking at the specific use of Torodal(ketorolac) in the perioperative phase of breast surgery. The initial study was from Belgium. This study is known as the Forget study published in 2010. A particular isolated group of patients that had an unusually low rate of breast cancer recurrence. All had the same breast surgeon and one of two anesthesiologist. The anesthesiologists had a common approach to drugs used for surgery.
Toradol was the common drug given intraoperative.(in surgery---common practice worldwide) Toradol is an NSAID. Your first reaction is that it is contraindicated for surgery. It does have risk, but the risk is outweighed by the benefit. As I stated earlier Toradol is commonly used by Anesthesiologist in the intraoperative phase of surgery.
My suggestion for anyone having surgery is different than my usual that science has to prove that this works. Talk with your surgeon and anesthesiologist pre-op. Ask specifically if they're is any reason that Toradol is contraindicated for use with you. There ARE patients that it should not be given too. With these studies in hand explore the use of Toradol intraoperatively. This drug is so routinely used in surgery, the question is not out of bounds.
Because we in the BC community experience so many surgeries, the pre-op instructions are drilled into our brains. No NSAIDS two weeks before and after. This though is different. The Retsky study had my heart racing and my breathing short. Studies can be difficult to read, but this is too exciting not to drink in every word. Sas-Schatzi
This link is to an article about the Forget et al study, 2010 patient cohort 327
Forget et all study----this will be/ is a landmark study
This is a link to Retsky et all study also will be/is a landmark study. It is a broader based analysis. Gives a great description of the inflammatory process and the impact on awakening a distant mets and killing circulating cancer cells and how Toradol influences these.
Forget et all study 2014 follow up from the 2010study, cohort 720
The amount and timing recommended by Dr.Patrice Forget is 20 mg preincisional in patients under 60 kg, and 30 mg in patients over 60 kg.
Quotes from Retsky's study
Using Computer Simulation to Analyze Bimodal Relapse Pattern
Based on computer simulation, to explain the 10 month peak we postulated that induction of angiogenesis at the time of surgery provoked sudden exits from dormant avascular phases to active growth and then to detection. That mode is quite sharp and most often seen among premenopausal patients with axillary lymph node involvement (N+). We suggested the remainder of relapses within the first 40 or so months to be surgery-induced growth of previously dormant single malignant cells. We proposed that the broad late peak relapses result from steady stochastic progressions from single dormant malignant cells to avascular micro-metastases and then on to growing deposits with no apparent synchronization to the time of surgery.
Most Important Finding – Early Relapses are the Result of Something that Happens at Surgery
The most important finding of this early work is that something happens at or about the time of surgery to accelerate or induce metastatic activity that results in early relapses. These early relapses comprise over half of all relapses. Surgery-induced angiogenesis of dormant avascular micrometastases and surgery-induced activity of single malignant cells are implicated. Late relapses are apparently not accelerated by surgery but the shallow peak at 5 years occurs as a result of shedding from primary ceasing after primary removal. We have been vigilantly looking for new data with which we can learn more about surgery-induced tumor activity and that perhaps will also lead to improved outcomes. As we describe here, there has been an important development.
Forget et al.  data from Universite catholique de Louvain in Brussels, Belgium. Relapse hazard is shown for mastectomy patients given ketorolac or not. Data are smoothed as indicated for fig. fig.11.
Forget et al. data were updated September 2011 and shown in hazard form but not smoothed as in fig. fig.7.7. Patient data are presented in the table. Patients included in this figure were less than 80 years of age, tumor less than 9 cm diameter and disease free survival greater than 2 months. It can be seen that relapses in months 9 -18 accounted for the major difference between ketorolac and non-ketorolac patients.
Very often the excuse to not use Toradol is because of concern about postop bleeding. Here are links and abstracts related to actual studies re: Toradol and postop bleeding.
See comment in PubMed Commons belowPlast Reconstr Surg.
2014 Mar;133(3):741-55. doi: 10.1097/01.prs.0000438459.60474.b5. Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials.
Gobble RM1, Hoang HL, Kachniarz B, Orgill DP. Author information
- 1Boston, Mass.; and New York, N.Y. From the Harvard Plastic Surgery Combined Residency Program and the Division of Plastic Surgery, Brigham & Women's Hospital, and Harvard Medical School; and New York University Langone Medical Center.
Postoperative pain control is essential for optimal patient outcomes. Ketorolac is an attractive alternative for achieving pain control postoperatively, but concerns over postoperative bleeding have limited its use.
Computer searches of the MEDLINE, EMBASE, and Cochrane Library databases were performed. Twenty-seven double-blind, randomized, controlled studies were reviewed by two independent investigators for the incidence of adverse events, including postoperative bleeding. Comprehensive meta-analysis software was used to evaluate the differences between ketorolac and control groups.
Twenty-seven studies with 2314 patients were analyzed. Postoperative bleeding occurred in 33 of 1304 patients (2.5 percent) in the ketorolac group compared with 21 of 1010 (2.1 percent) in the control group (OR, 1.1; 95 percent CI, 0.61 to 2.06; p = 0.72). Adverse events were similar in the groups, 31.7 percent in the control group and 27.9 percent in the ketorolac group (OR, 0.64; 95 percent CI, 0.41 to 1.01; p = 0.06). There was a lower incidence of adverse effects with low-dose ketorolac (OR, 0.49; 95 percent CI, 0.27 to 0.91; p = 0.02). Pain control with ketorolac was superior to controls and equivalent to opioids.
This is the first meta-analysis of randomized controlled trials examining whether there is increased postoperative bleeding with ketorolac. Postoperative bleeding was not significantly increased with ketorolac compared with controls, and adverse effects were not statistically different between the groups. Pain control was found to be superior with ketorolac compared with controls. Ketorolac should be considered for postoperative pain control, especially to limit the use of opioid pain medications.
CLINICAL QUESTION/LEVEL OF EVIDENCE:
Plast Reconstr Surg. 2001 Feb;107(2):352-5.
Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction.
Sharma S1, Chang DW, Koutz C, Evans GR, Robb GL, Langstein HN, Kroll SS. Author information
- 1Department of Plastic Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.
This study states a three fold increase in hematoma formation after a reduction mammoplasty. if you evaluate the numbers sited in the study in the are small in actual occurrence, but when the phrase "three fold increase" is used in the conclusion of the actual study and then repeated in the abstract, the implication is the numbers are ominous. Another way the authors of the study describe the risk is a 1:16 ratio. When the risk of recurrence is balanced against the hematoma risk, the reduction in recurrence should be weighted in favor of disease free survival
Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty.
We conducted a retrospective review following concerns involving a suspected increase in the requirement for surgical re-exploration for hematoma evacuation when ketorolac was administered perioperatively in patients undergoing reduction mammoplasty.
Following ethics approval, a retrospective chart review was conducted of all patients who underwent reduction mammoplasty at our two institutions from the time ketorolac became available in 2004 until surgeons requested its use discontinued in 2007. The data we collected included patient demographics, ketorolac administration, requirement for surgical re-exploration, documented hematoma formation not requiring surgical re-exploration, and excessive bleeding in the perioperative period. Three hundred and seventy-nine patient records were reviewed; 127 of the patients received a single intravenous dose of ketorolac (15 or 30 mg), and 252 of the patients did not receive ketorolac.
Patients who received ketorolac were at an increased risk of requiring surgical re-exploration for hematoma evacuation (relative risk [RR] = 3.6; 95% confidence interval [CI], 1.4 to 9.6) and hematoma formation not requiring re-exploration (RR = 2.2; 95% CI, 1.3 to 3.6).
A single perioperative intravenous dose of ketorolac was associated with a greater than three-fold increase in the likelihood of requirement for surgical hematoma evacuation. Our data suggest that it may be prudent to consider carefully whether the potential risks associated with the use of ketorolac outweigh the potential benefits of using ketorolac in patients undergoing reduction mammoplasty.
This is an alternative letter for your Doc and anesthiologist written by Falleaves. At first I was going to delete mine above, but on a reread they're is good info that's not covered in Falls letter. So, I'm leaving mine and adding hers.
Nov 23, 2015 10:26AM - edited Nov 23, 2015 11:47AM by sas-schatzi
Geewhiz, Falls sent me a copy of a letter she wrote to her old doc. I asked that she revise it and post here. I would then erase the old doc letter from page 1 or pg 2. Time is short. Just in case Falls doesn't see your post, I'm reposting part of it. It's really well done :)
Written by Falleaves November 2015
Summarizing the papers I have read, inhaled anesthetics and opioids should be avoided because of their immunosuppressive effects. Opioids have also been implicated in increasing angiogenesis. Total intravenous anesthesia (TIVA) with propofol (which may reduce postoperative nausea) seems to suppress the inflammatory response to surgery. COX-2 inhibitors and NSAIDS, in particular preoperative ketorolac, could also reduce recurrence due to their anti-inflammatory properties, and their reduction of the need for opioids. Paravertebral nerve block (frequently with propofol) may be particularly valuable in reducing inflammatory cascades and preserving immune function, and reducing recurrence. It also provides better pain control than general anesthesia, reducing the need for opioids post surgery. Local anesthetics such as lidocaine and bupivicaine have been shown to cause apoptosis in breast cancer cells, and liposomal bupivacaine can provide good postsurgical analgesia and reduce the need for opioids. Preoperative gabapentin and pregabalin are effective in reducing postoperative pain and opioid use, and is preventive for chronic post surgical pain.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615712/
Interestingly, many of the anesthetic choices that appear most likely to reduce recurrence, are also better for overall patient well-being. You may be familiar with enhanced recovery pathways. Johns Hopkins has developed an ERP for colorectal patients: "The goals of the perioperative anesthesiology pathway were achieving superior analgesia, minimizing postoperative nausea and vomiting, facilitating patient recovery, and preserving perioperative immune function...The perioperative anesthetic regimen was tailored to meet the goal of perioperative immune function (in an attempt to decrease surgical site infection and decrease cancer recurrence), in part by minimizing perioperative opioid use." http://www.ncbi.nlm.nih.gov/pubmed/26404073 The Mayo Clinic has created an ERP for breast reconstruction operations, as well. This includes preoperative analgesics and preventive nausea treatment, NSAIDS, liposomal bupivacaine, reduction in opioids post surgery, and resumption of eating and walking soon after surgery. http://newsnetwork.mayoclinic.org/discussion/new-approach-to-breast-reconstruction-surgery-reduces-opioid-painkiller-use-hospital-stays/
It is my thought that if you are talking about a wide range of drugs and techniques that have ALL been tested, approved, and are in wide use, it is wise to favor those that do not promote the growth of cancer. Clearly anesthetics need to be tailored to each patient, but the impact on cancer recurrence should be a factor in the equation. It would be beneficial for breast cancer patients if an enhanced recovery pathway could be developed for them, with particular attention to use of drugs and techniques to reduce the chance of recurrence.
You are a very busy person, and I realize anesthesia is not your area, but as the director of the Breast Center you are in a position to influence every aspect of care. I am linking some of the best studies I have found, and hope that you will share them with your anesthesiologists.
"Can anesthestic technique for primary breast cancer surgery affect recurrence or metastasis?"
"Efficacy and safety of paravertebral blocks in breast surgery: a meta-analysis of randomized controlled trials."
"Anesthesia technique may reduce breast cancer recurrence, death."
"Thoracic paravertebral regional anesthesia improves analgesia after breast cancer surgery: a controlled randomized multicentre clinical trial"
"Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery."
"Reduction of Breast Cancer Relapse with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review"
"Local anesthetics induce apoptosis in breast cancer cells"
"Evolving Role of Local Anesthestics in Managing Postsurgical Analgesia."
Gabapentin and Pregabalin
"The Prevention of Chronic Postsurgical Pain Using Gabapentin and Pregabalin: A Combined Systemic Review and Meta-Analysis"
Review articles on Anesthesia and Cancer
"The effects of anesthesia on tumor progression"
"Are we causing the recurrence-impact of perioperative period on long-term cancer prognosis: Review of currrent evidence and practice"
Life's journey is not to arrive at the grave safely in a well preserved body, but rather to skid in sideways, totally worn out shouting "holy crap....what a ride".